This is a program of multidisciplinary clinical studies of factors influencing the development of and loss of tolerance and dependence to opiates, barbiturates, and other neurotropic drugs in humans. Clinical evaluation of the effects of various antagonists and detoxification schemes and agents will be used to assess the effectiveness of psychosocial and chemical interventions in changing drug seeking behavior as drug dependent patients are followed over time. In addition to measures of behavioral change, a number of laboratory studies will focus on common groups of patients. These include neurophysiologic studies with EEG and evoked potentials, studies of autonomic function, studies of drug metabolites and the pharmacokinetics of morphine, methadone and naloxone so as to better understand behavioral and physiologic changes during acute and protracted abstinence.